The long-term objective of this laboratory work is to identify nutritional factors which contribute to the high incidence of colon cancer in Western culture. In this proposal, studies are focused on the role of dietary and endogenous cholesterol and its metabolites in the gut lumen in large bowel tumorigenesis in an experimental animal. Continuing studies are planned on the interrelationship between dietary polyunsaturated fat and saturated fat, particularly as it relates to the disbursement of cholesterol systemically and/or enterally. Various nutritional regimens containing 20% fat with and without cholesterol are fed to rats given an indirect acting carcinogen, 1,2 dimethylhydrazine (s.c. or orally), or a direct acting carcinogen, N-methyl-N'-nitro-N-nitroguanidine (intrarectally). These diets will allow an evaluation of the interrelationships between the quality of dietary fat, the enteral excretion of cholesterol and its metabolites and large bowel tumorigenesis. Effects of cholesterol and its metabolites will be evaluated in terms of tumor number, histological types and location, latency period and tumor incidence. An assessment of fecal excretion of neutral and acid sterols as well as fecal 7-alpha-dehydroxylase and cholesterol dehydrogenase activities occurring in rats fed the various dietary regimes will permit correlative studies with large bowel tumorigenesis. Using the Ames Salmonella/microsomal assay for mutagens/carcinogens, various fecal sterol metabolites will be evaluated to pinpoint those componets which may be carcinogenic or cocarcinogenic for further testing. These studies should provide: 1) a better understanding of the relationships between nutrition, microflora and colonic cancer; 2) additional information concerning the nutritional linkage between coronary heart disease and colon cancer and 3) additional guidelines for studies in human nutrition aimed at decreasing the incidence of colon cancer.